Ten-Year Review of Gestational Trophoblastic Disease at Lady Reading Hospital, Peshawar.

OBJECTIVE: To determine the frequency and management outcome of gestational trophoblastic disease (GTD) in Lady Reading Hospital. METHODS: This was a retrospective observational study at Lady Reading Hospital, Peshawar, from January 2011 to December 2021. Hospital records of all patients with GTD were reviewed and all were included in this study except those with an incomplete record or unconfirmed histology. Treatment was analysed in terms of surgical, chemotherapy or no treatment, and outcomes were noted in terms of complete remission, disease persistence or death. RESULTS: In 10 years 353 patients were admitted with GTD, and the frequency of the disease was 3.72 cases per 1000 pregnancies. The most frequent lesions were complete mole 65.2% (n=230) followed by invasive mole 20.4% (n=72). Mortality rate was 0.56% (n=2). Maternal blood group analysis revealed that B positive 28.3% (n=100) was more frequent. O positive blood group was found more in the malignant form of the disease at 3.96% (n=14). GTD was most prevalent in 21 to 30 years of age (41.4%, n=146). Regarding treatment, in 69.97% (n=247) of cases, suction and evacuation were performed, in 4.2% (n=15) of cases hysterectomy was performed as primary therapy, and 4.8% (17) needed hysterectomy for chemoresistance. In this study 42.49% (n=150) were given single-agent chemotherapy and 4.8% (n=17) were given multi-agent therapy. We had 21.33% (32) patients with a risk score of 7-9. In the group with a risk score of 7-9, 15.62% (n=5) patients were directly started on multi-agent therapy because of evidence of metastasis or choriocarcinoma; the remaining 84.37% (n=27) of patients who had no evidence of metastasis, no prior chemotherapy, no choriocarcinoma and International Federation of Obstetrics and Gynecology (FIGO) stage 1 were given single-agent methotrexate with folinic acid (eight days) after informed consent. In 18.75% of patients (n=6) hysterectomy was performed as the primary treatment either for haemorrhage or with age > 40, family completed, or reluctance to undergo chemotherapy. They all had a complete cure. In 3.1% (n=1) of cases, resistance to single-agent therapy was found and multi-agent treatment was started. Overall, in 96.29% of patients, complete remission was achieved with single-agent therapy in patients with risk scores of 7-9. CONCLUSION: The frequency of GTD was 3.4/1000 pregnancies. Complete mole was the most frequent lesion, and single-agent chemotherapy had a good outcome in low- and high-risk patients with a risk score of 7-9 (with no evidence of metastasis, prior chemotherapy, or choriocarcinoma and FIGO stage 1).

Monitoring outcomes in children with acquired brain injury (ABI): a Persian validation study of Child and Family Follow-up Survey (CFFS).

AIM: To translate and validate the Child and Family Follow--up Survey (CFFS) in Iran. METHODS: 49 cases with Acquired Brain Injury (ABI), and 30 healthy children were included and the CFFS was completed. The Pediatric Quality of Life Inventory (PedsQL) also was completed. The internal consistency, test-retest reliability, known groups comparison and criterion validity were assessed. RESULTS: The mean age of participants was 10.9 years. Cronbach's alpha coefficients were Child and Adolescent Scale of Participation (CASP) (0.91), Child and Adolescent Factors Inventory (CAFI) (0.90) and Child and Adolescent Scale of Environment (CASE) (0.89). Reliability, validity and correlation of CASP and CAFI showed satisfactory results. Significant correlations among the three CFFS subscale scores were observed. These scores were also significantly correlated with the total scores of the PedsQL. CONCLUSION: The findings suggest that CFFS is a valid measure to monitor long--term outcomes of children and young adolescents with ABI.

Finding Novel Anti-carcinomas Compounds by Targeting SFRP4 Through Molecular Modeling, Docking and Dynamic Simulation Studies.

BACKGROUND: Secreted Frizzled-Related Protein 4 (SFRP4) is a glycoprotein that acts as a competitor of both canonical and non-canonical Wnt pathways. SFRP4 is mostly expressed in ovary and plays a significant role as a target molecule to cure ovarian carcinoma. OBJECTIVE: Multiple chemical agonists are being used to cure ovary melanoma. We are interested in theoretically analyzing the compounds through computational approaches for their potential inhibitory effects against SFRP4. METHODS: Compounds were sketched in Chemsketch drawing tool and minimized through chimera tool. Because the crystal structure of SFRP4 is not available in Protein Data Bank, homology modeling approach was used to predict Three-Dimensional (3D) crystal structure of SFRP4. Moreover, multiple computational approaches such as molecular docking and Molecular Dynamic (MD) simulations along with various online tools were employed to screen the best inhibitor against ovary melanoma. RESULTS: The docking results showed that 1d and 1e compounds revealed significant binding energy values (-9.10 and -9.00 kcal/mol, respectively) compared with the standard drugs such as cis-platin and docetaxel (-3.30, -10.80 kcal/mol), respectively. Moreover, MD simulation results showed that 1d has little fluctuations throughout the simulation period as depicted by the root mean square deviation and root mean square fluctuation graphs. CONCLUSION: The present in-silico study provides a deeper insight into the structural attributes of 1d compound and its overall molecular interactions against SFRP4 and gives a hypothetical gateway to use this compound as a potential inhibitor against ovarian carcinoma.

Enhanced susceptibility of obese mice to glycidamide-induced sperm chromatin damage without increased oxidative stress.

Diet-induced obesity is known to impair male reproduction and may aggravate the male reproductive toxicity of the food contaminant acrylamide. Exposure of male mice to acrylamide induces paternally mediated pre- and post-implantation losses because of spermatozoal toxicity and these effects are potentiated in mice fed a high-fat diet. Glycidamide - an acrylamide metabolite - is the primary mediator of reproductive effects in males. The mechanisms causing the interaction between diet and acrylamide are not clear. However, diet-induced obesity is associated with oxidative stress in male reproductive tissues which might contribute to increased germ cell susceptibility. In this study, we investigated whether a moderate diet-induced obesity regimen could interfere with glycidamide-induced spermatozoal toxicity and increase oxidative stress. For this purpose, sperm chromatin integrity, oxidised DNA and protein levels, transcript levels of oxidative stress responsive genes and glycidamide-induced DNA and haemoglobin adducts were analysed in samples from male mice exposed to a high-fat diet for 6 weeks in combination with a single glycidamide exposure 7 days prior to sacrifice. We found that glycidamide-induced sperm DNA fragmentation was markedly higher in obese than in lean mice. However, the levels of oxidised DNA and/or protein in blood, liver and testicular tissue was lower in obese than in lean mice. Accompanying the reduced level of oxidised macromolecules, the transcript levels of several oxidative stress-related genes were altered in the liver and testis from obese mice suggesting induction of an antioxidant response in these animals. The haemoglobin-glycidamide adduct levels were higher in obese than in lean animals, whereas obesity did not seem to increase the level of glycidamide-induced DNA adducts. These findings show that a moderate diet-induced obesity regimen may potentiate glycidamide-induced sperm cells toxicity and suggest that the increase in glycidamide-induced sperm toxicity observed in obese mice does not depend on overt oxidative stress.

Tactile discrimination task not disturbed by thalamic stimulation.

The major pathway of human somatosensation passes through the ventrocaudal nucleus (Vc) of the thalamus. We tested the effect of direct electrical stimulation of the Vc on tactile discrimination in 5 Parkinson patients undergoing stereotactic thalamotomy. Raised gratings with lines 3, 4, or 6 mm apart were used. Patients had to actively touch test patterns placed in the hand contralateral to the thalamus under operation and compare it with a reference 3-mm grating held continuously in their other hand. Their performance was best for 6-mm, followed by 3-mm and then by 4-mm patterns regardless of electrical stimulation. Under Vc stimulation, patients recognized the 4-mm gratings slightly better. This can be explained either by the nature of thalamocortical interaction, which makes it resistant to external noise, or by the involvement of other pathways that circumvent the effect of thalamic stimulation.

Stereotactic management of bacterial brain abscesses.

BACKGROUND: CT and MR guided stereotactic techniques have provided promising results in the management of brain abscesses. We reviewed our results of stereotactic management of brain abscesses in 20 consecutive patients with 28 abscesses from 1986 to 1993. METHODS: 13 abscesses were in the cerebral hemispheres, 12 in the cerebellum, 2 in the pons and 1 in the thalamus. The bacterial organism was isolated in 12 of the 20 cases. All patients, except one who had a tuberculous abscess, were on antibiotics for less than 7 weeks. RESULTS: Although there were 3 patients in coma before surgery, the mortality rate was zero and 17 patients had an excellent recovery with 3 patients having a persistent mild neurologic disability. Stereotactic aspiration of the largest lesion in the patients with multiple brain abscesses combined with intravenous antibiotic therapy was sufficient for the resolution of all lesions. Two of our patients treated with antibiotics alone showed abscess progression with neurologic worsening. CONCLUSION: Stereotactic aspiration is safe, accurate, and when combined with the appropriate antibiotics, should be considered the procedure of choice in the management of brain abscesses.

Thalamotomy for essential and cerebellar tremor.

Thalamotomy significantly suppressed essential tremor in 86% of patients and restored the ability to hold a glass to drink in 81% in the long term, but tremor recurred in 5/21 patients up to 5 years postoperatively, unlike parkinsonian patients whose tremor seldom recurs after 3 months. In multiple sclerosis (MS), 67% of those followed showed sustained significant suppression of tremor, 67% sustained improvement in dexterity, 50% in drinking; tremor recurred up to 5 years postoperatively. In other cerebellar tremors, 52% of those followed enjoyed lasting significant relief of tremor, 55% in dexterity, 45% in drinking, tremor relief being best in poststroke cases. Chronic thalamic stimulation may be the preferred therapy in MS and other cerebellar tremors.